Long-chain omega-3 fatty acids are available primarily via consumption of fish and are known to serve many important roles in cell function and body homeostasis. Furthermore, these micronutrients reduce cardiovascular disease (CVD) events when supplemented in the diets of patients with pre-existing heart disease. Given that Americans currently consume an average of only 120 mg of long-chain omega-3 fatty acids each day,the American Heart Association now recommends now recommends that all adults eat fish, particularly fatty fish, as least twice a week. As yet there is little direct evidence to support such an advisory since it is not clear either whether or how increasing fish consumption in the diet of the general pubic will reduce the risk of heart disease. In separate research, a relative deficiency in the omega-3 fatty acids has been associated with major depression, attention-deficit disorder and aggressive behavior in forensic samples. Once again, studies in healthy adults are lacking. Project 3 of this Program Project Grant application proposes to conduct two investigations, an observational study of 530 generally-healthy community volunteers 30-55 year of age,and,in a subset reporting low consumption of omega-3 fatty acids, a placebo-controlled supplementation experiment of 4 months duration. In both studies, markers of cardiovascular risk will be measured, as will psychological and behavioral characterises that have previously been linked to heart disease and omega-3 fatty acid availability. In addition, the observational study will include carotid ultrasound as a measure of pre-clinical atherosclerosis and functional brain imaging of regions regulating affect/threat detection and impulsivity/goal-directed behaviors. The research will test the hypotheses that high or raised EPA and DMA intake: 1) reduces CVD risk, 2) reduces depressive symptoms and antagonistic disposition, 3) reduces impulsivity and aggression, and 4) is related to activation of neural structures involved in affect and goal- directed behaviors. Finally, the effects of variation in genes regulating fatty acid metabolism will be studied. Relevance: CVD remains a leading cause of death and disability, and the search for new preventative interventions remains a prioty. Increasing fish and fish oil consmption appears to reduce mortality in patients with prexisiting heart disease and may have salutory effects on psychological health and well-being. The proposed research will more clearly establish whether fish oil supplementation reduces heart disease risk factors and is associated with other benefial effects on mood, antagonsitic disposition and impulsivity.